Originally published as JCO Early Release 10.1200/JCO.2008.18.9498 on August 31 2009

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Presence of Intratumoral Neutrophils Is an Independent Prognostic Factor in Localized Renal Cell Carcinoma

From the Departments of Oncology, Experimental Clinical Oncology, and Urology, Aarhus University Hospital, Aarhus; Department of Clinical Pathology, Odense University Hospital, Odense; Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Corresponding author: Hanne Krogh Jensen, MD, PhD, Department of Oncology, Aarhus University Hospital, Noerrebrogade 44, 8000 Aarhus C, Denmark; e-mail: hajensen{at}rm.dk.

Purpose We have previously demonstrated a significant negative impact of intratumoral neutrophils in metastatic renal cell carcinoma. This study assessed intratumoral neutrophils in localized clear cell renal cell carcinoma (RCC).

Patients and Methods The study comprised 121 consecutive patients who had a nephrectomy for localized RCC. Biomarkers (intratumoral CD8+, CD57+ immune cells, CD66b+ neutrophils, and carbonic anhydrase IX [CA IX]) were assessed by immunohistochemistry, and the relationship with clinical and histopathologic features and patient outcome was evaluated.

Results The intratumoral neutrophils ranged from zero to 289 cells/mm² tumor tissue. The presence of intratumoral neutrophils was statistically significantly associated with increasing tumor size, low hemoglobin, high creatinine, and CA IX 85%. In multivariate analysis, the presence of intratumoral neutrophils (hazard ratio [HR], 3.0; 95% CI, 1.7 to 5.4; P < .0001), pT stage T3b/T4 (HR, 2.1; 95% CI, 1.2 to 3.6; P = .007), and low hemoglobin (HR, 1.8; 95% CI, 1.0 to 3.1; P = .03) were independent prognostic factors significantly associated with short recurrence-free survival. The presence of intratumoral neutrophils was also an independent prognostic factor for cancer-specific survival (HR, 3.5; 95% CI, 1.9 to 6.4; P < .0001) and overall survival (HR, 3.1; 95% CI, 1.9 to 5.0; P < .0001). Applying the prognostic value of intratumoral neutrophils to the Leibovich low-/intermediate-risk group (n = 78) showed a 5-year recurrence-free survival of 53% (95% CI, 34.6% to 71.8%; presence of intratumoral neutrophils) versus 87% (95% CI, 77.8% to 96.8%; absence of intratumoral neutrophils). The estimated concordance index was 0.74 using the Leibovich risk score and 0.80 when intratumoral neutrophils were added.

Conclusion The presence of intratumoral neutrophils is a new, strong, independent prognostic factor for short recurrence-free, cancer-specific, and overall survival in localized clear cell RCC.

Supported by Aarhus University Hospital Research Initiative; Max and Inger Wørzner Foundation; Frits, Georg, and Marie Cecilie Glud Foundation; and Aarhus Radium Center Research Foundation.

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

Presented in part at the 7th International Kidney Cancer Symposium, September 26-27, 2008, Chicago, IL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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